The lymphocytes from animals immune to syngeneic Simian virus 40 (SV40)-induced tumors recognize both virus-induced and Histocompatibility-2 (H-2) antigens on SV40 transformed target cells. Evidence presented here suggests that T cells bind to a complex between H-2 and the viral antigen on the tumor cell, and formation of this complex is necessary, if not sufficient, for induction of cytolytic T cells and for in vitro tumor destruction by T cells. In the work proposed, we will investigate the formation of antigen complexes in the tumor cell plasma membrane and the relationship between complex formation and immune T cell recognition. Co-capping of tumor-associated antigens with mouse H-2 antigens, reported by this and other laboratories, also indicates physical associations among plasma membrane molecules. We have recently found that antigens which co-cap can also be extracted from the membrane as specific complexes. Both the murine leukemia virus gp71 and a carcinofetal antigen, Ag I, are associated with the H-2 antigens following solubilization of L cell membranes with low concentrations of non-ionic detergents. We will study the requirements for formation of these complexes and the relationship between complex formation and endogenous virus production. We will establish a model system for T cell recognition of foreign proteins expressed on syngeneic cells. This model will allow quantitative evaluation of immune recognition and manipulation of the immune response to cell surface antigens.